title: Serum androgens as prognostic biomarkers in castration-resistant prostate cancer: results from an analysis of a randomized phase III trial.
abstract: OBJECTIVE
  In the phase III study COU-AA-301, abiraterone acetate (AA) plus prednisone (P) prolonged overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) after docetaxel administration. In this article, we investigate the relationship between baseline serum androgen (SA) levels and OS.
  
  
  METHODS
  COU-AA-301 is a randomized, double-blind study of AA (1,000 mg every day) plus P (5 mg by mouth twice daily; n = 797) versus P alone (n = 398). Randomization was stratified by Eastern Cooperative Oncology Group performance status (0 to 1 v 2), pain (Brief Pain Inventory-Short Form over past 24 hours: 4 to 10, present; v 0 to 3, absent), prior chemotherapy (1 v 2), and progression (prostate-specific antigen v radiographic). Association of baseline SA (testosterone, androstenedione, dehydroepiandrosterone sulfate), was measured by ultrasensitive liquid-liquid extraction or protein precipitation and two-dimensional liquid chromatography coupled to mass spectrometry, with OS determined by bivariate and multivariable Cox models. OS was examined with SA as greater than median and less than or equal to the median.
  
  
  RESULTS
  Median survival increased with each quartile increase in testosterone level regardless of treatment arm. SA levels at baseline strongly associated with survival (P < .0001) in bivariate and multivariable analyses. Longer survival was observed for patients with SA above median compared with below median in both the AA and P arms (eg, testosterone, AA; hazard ratio, 0.64; 95% CI, 0.53 to 0.77; P < .0001). Treatment with AA led to longer survival versus P alone in the above- or below-median group for all androgens.
  
  
  CONCLUSIONS
  SA, measured with a novel ultrasensitive assay in COU-AA-301, is prognostic for OS and may be useful for risk stratification in mCRPC clinical trials.
authors.affiliation: University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA 94115, USA. ryanc@medicine.ucsf.edu
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Ryan
authors.forename: Arturo
authors.initials: A
authors.lastname: Molina
authors.forename: Jinhui
authors.initials: J
authors.lastname: Li
authors.forename: Thian
authors.initials: T
authors.lastname: Kheoh
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Small
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Haqq
authors.forename: Russell P
authors.initials: RP
authors.lastname: Grant
authors.forename: Johann S
authors.initials: JS
authors.lastname: de Bono
authors.forename: Howard I
authors.initials: HI
authors.lastname: Scher
mesh_terms: D000069501:Abiraterone Acetate; D000728:Androgens / Q000097:blood*; D000730:Androstadienes / Q000008:administration & dosage*; D004311:Double-Blind Method; D006801:Humans; D059625:Liquid-Liquid Extraction; D008297:Male; D009919:Orchiectomy; D011241:Prednisone / Q000008:administration & dosage*; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology; D013739:Testosterone / Q000097:blood
chemical_list: D000728:Androgens; D000730:Androstadienes; D013739:Testosterone; D000069501:Abiraterone Acetate; D011241:Prednisone